A case series of fluoroscopy-guided neurolytic splanchnic nerve block for chronic pancreatitis pain.

Context: Splanchnic nerve block (SPN) with local anesthetic and steroid is used to relieve the pain of chronic pancreatitis. However, it does not provide long-lasting relief. We hypothesize that the use of 70% alcohol will give adequate analgesia for more than months. Aims: The primary objective was to find out the analgesic efficacy of the use of 70% alcohol with SPN. Secondary objectives included the incidence of side effects, analgesic consumption postintervention, quality of life (QOL) assessed via a self-reported quality of life scale, and repeat block during the 1-year follow-up period. Settings and Design: Retrospective analysis of all patients with chronic pancreatitis who received bilateral SPN over the last 4 years. Methods and Materials: SPN was performed using the posterior retrocrural approach with the patient in the prone position as described in the literature using a 23 G × 90 mm spinal needle bilaterally at the level of T12 using C-arm/fluoroscopy guidance. Data were collected from the procedure book of the pain clinic and medical records. Statistical Analysis Used: Quantitative data for change in pre- to post-block VAS score was collected using the non-parametric Wilcoxon signed ranks test. Results: The baseline VAS, post-procedure VAS, and VAS at 3 months follow-up was 7.69 ± 1.3,2.44 ± 0.96 and 1.56 ± 1.15. A pairwise comparison of VAS performed between baseline and immediate post-procedure, baseline, and VAS at 3 months was found to be highly significant. Conclusions: Fluoroscopy-guided neurolytic SPN with 70% alcohol gives significant pain relief for more than 3 months. It also leads to improvement in 3 months QOL.

Evaluation of a multiphase cascaded H-bridge inverter for induction motor operation.

Multi-phase systems are becoming more popular for applications requiring high power and precise motor control, even if single-phase AC power is still frequently utilized in households and some enterprises. While both systems have benefits over single-phase, there are trade-offs associated with each. Because of its balanced operation and effective power transfer, the three-phase (3-Φ) system is the most widely used multi-phase system. Nevertheless, different phase values can be investigated for particular applications where reducing torque ripple and harmonic content is essential. Using odd numbers of phases (such as 5-Φ) that are not multiples of three is one method. This design has the ability to reduce torque ripple by producing a more balanced magnetic field as compared with even-numbered phases. But adding more phases also makes the system design and control circuitry more complex. Systems with five phases (5-Φ) provide a compromise between performance and complexity. Applications such as electric ship propulsion, rocket satellites, and traction systems may benefit from their use. Nevertheless, choosing a multi-phase system necessitates carefully weighing the requirements unique to each application, taking into account elements like cost, power transmission, control complexity, and efficiency. The increasing popularity of electric vehicles and renewable energy technologies has led to the need for inverters in current electric applications. Conventional inverters provide square wave outputs, which cause the drive system to become noisy and cause harmonics. Multi-phase multilevel inverters can be used to enhance inverter functioning and produce an improved sinusoidal output. This study focuses on an induction motor drive powered by a five-phase multilevel cascaded H-Bridge inverter. With less torque and current ripples in the motor rotor, the power conversion harmonics are reduced and the switching components of the inverter are under less stress. However, in comparison to traditional inverters, it does require a greater number of legs. Because the switches needed for the cascaded H-Bridge inverter are less expensive in five-phase systems, they are favoured over higher phase orders. Furthermore, the suggested inverter removes 5th order harmonics, something that is not possible with traditional inverters. A five-phase induction motor appropriate for variable speed driving applications is also suggested by this research. Lastly, utilizing pulse width modulation (PWM) converters and an FPGA controller, an experimental study is carried out to assess the dynamic performance of the suggested induction motor drive. Particular attention is paid to the In-Phase Opposition Disposition (IPD) PWM technique.

Hybrid genetic algorithm-simulated annealing based electric vehicle charging station placement for optimizing distribution network resilience.

Rapid placement of electric vehicle charging stations (EVCSs) is essential for the transportation industry in response to the growing electric vehicle (EV) fleet. The widespread usage of EVs is an essential strategy for reducing greenhouse gas emissions from traditional vehicles. The focus of this study is the challenge of smoothly integrating Plug-in EV Charging Stations (PEVCS) into distribution networks, especially when distributed photovoltaic (PV) systems are involved. A hybrid Genetic Algorithm and Simulated Annealing method (GA-SAA) are used in the research to strategically find the optimal locations for PEVCS in order to overcome this integration difficulty. This paper investigates PV system situations, presenting the problem as a multicriteria task with two primary objectives: reducing power losses and maintaining acceptable voltage levels. By optimizing the placement of EVCS and balancing their integration with distributed generation, this approach enhances the sustainability and reliability of distribution networks.

A novel strategy towards efficient and reliable electric vehicle charging for the realisation of a true sustainable transportation landscape.

This paper proposes an innovative approach for improving the charging efficiency of electric vehicles (EVs) by combining photovoltaic (PV) systems with AC-DC Power Factor Correction (PFC). The proposed approach employs bi-directional power flow management within the PFC system, allowing for enhanced resource utilization and EV battery capacity under a variety of environmental circumstances. A modified Lyapunov-based robust model reference adaptive controller (M-LRMRAC) is developed to provide real-time Maximum Power Point Tracking (MPPT) for the PV array. By quickly recording the MPP, this controller skilfully adjusts to shifting radiation and temperature dynamics. A noteworthy accomplishment is that the M-LRMRAC outperforms traditional Perturb and Observe (P&O) techniques by achieving quick MPP convergence (0.54 s). Additionally, the benefits of this integrated system go beyond effective MPPT. The method achieves operating at unity power factor and reduces total harmonic distortion, which results in improved power quality when charging EV Batteries (EVB). The entire solution provided by this multifaceted architecture improves the quality of electricity delivered to EV batteries while also increasing energy efficiency. This research helps to the evolution of sustainable and dependable EV charging infrastructure by solving difficulties and optimising performance. The combination of PV systems with AC-DC PFC, aided by the M-LRMRAC technology, presents a viable route for attaining efficient, clean, and high-quality EV charging, hence supporting the shift to a greener and more sustainable transportation landscape.

A Novel Dynamic Bit Rate Analysis Technique for Adaptive Video Streaming over HTTP Support.

Recently, there has been an increase in research interest in the seamless streaming of video on top of Hypertext Transfer Protocol (HTTP) in cellular networks (3G/4G). The main challenges involved are the variation in available bit rates on the Internet caused by resource sharing and the dynamic nature of wireless communication channels. State-of-the-art techniques, such as Dynamic Adaptive Streaming over HTTP (DASH), support the streaming of stored video, but they suffer from the challenge of live video content due to fluctuating bit rate in the network. In this work, a novel dynamic bit rate analysis technique is proposed to model client-server architecture using attention-based long short-term memory (A-LSTM) networks for solving the problem of smooth video streaming over HTTP networks. The proposed client system analyzes the bit rate dynamically, and a status report is sent to the server to adjust the ongoing session parameter. The server assesses the dynamics of the bit rate on the fly and calculates the status for each video sequence. The bit rate and buffer length are given as sequential inputs to LSTM to produce feature vectors. These feature vectors are given different weights to produce updated feature vectors. These updated feature vectors are given to multi-layer feed forward neural networks to predict six output class labels (144p, 240p, 360p, 480p, 720p, and 1080p). Finally, the proposed A-LSTM work is evaluated in real-time using a code division multiple access evolution-data optimized network (CDMA20001xEVDO Rev-A) with the help of an Internet dongle. Furthermore, the performance is analyzed with the full reference quality metric of streaming video to validate our proposed work. Experimental results also show an average improvement of 37.53% in peak signal-to-noise ratio (PSNR) and 5.7% in structural similarity (SSIM) index over the commonly used buffer-filling technique during the live streaming of video.

NADH-depletion triggered energy shutting with cyclometalated iridium (III) complex enabled bimodal Luminescence-SERS sensing and photodynamic therapy.

The nicotinamide adenine dinucleotide-reduced (NADH) function as a hydride (H) carrier to maintain cellular homeostasis. Herein, we report a quinoline appended iridium complex (QAIC) as a molecular probe in fluorescence and surface-enhanced Raman spectroscopy (SERS) modalities to evaluate the endogenous NADH status. NADH-triggered activation of QAIC enabled luminescence (turn-ON) and SERS (turn-OFF) switching phenomenon with a detection limit of 25.6 nM and 15 pM for NADH in luminescence and SERS respectively. Transition state modelling using density functional theory calculations proved that a facile migration of H from NADH to QAIC transformed the activated QAIC (N-QAIC) with an energy span of 19.7 kcal/mol. Furthermore, N-QAIC is probed as a photosensitizer to source singlet oxygen by blocking the photo induced electron transfer (PeT) and generate NAD radicals. Therefore, an efficient light triggered cyclometalated iridium-based molecular probe has been divulged to promote bimodal NADH sensing and multiphase photodynamic therapy.

Dynamic self-assembly of mannosylated-calix[4]arene into micelles for the delivery of hydrophobic drugs.

Carbohydrate-lectin interactions and glycol-molecule-driven self-assembly are powerful yet challenging strategies to create supramolecular nanostructures for biomedical applications. Herein, we develop a modular approach of micellization with a small molecular mannosylated-calix[4]arene synthetic core, CA4-Man3, to generate nano-micelles, CA4-Man3-NPs, which can target cancer cell surface receptors and facilitate the delivery of hydrophobic cargo. The oligomeric nature of the calix[4]arene enables the dynamic self-assembly of calix[4]arene (CA4), where an amphiphile, functionalized with mannose units (CA-glycoconjugates) in the upper rim and alkylated lower rim, afforded the CA4-Man3-NPs in a controllable manner. The presence of thiourea units between calixarene and tri-mannose moiety facilitated the formation of a stable core with bidentate hydrogen bonds, which in turn promoted mannose receptor targeted uptake and helped in the intracellular pH-responsive release of antineoplastic doxorubicin (Dox). Physiochemical features including the stability of the nanomicelle could circumvent the undesirable leakage of the cargoes, ensuring maximum therapeutic output with minimum off-targeted toxicity. Most importantly, surface-enhanced Raman scattering (SERS) was utilized for the first time to evaluate the critical micelle concentration during the formation, cellular uptake and intracellular drug release. The present study not only provides an architectural design of a new class of organic small molecular nanomicelles but also unveils a robust self-assembly approach that paves the way for the delivery of a wide range of hydrophobic chemotherapeutic drugs.

Assessment of biogrowth assemblages with depth in a seawater intake system of a coastal power station.

Marine biogrowth infestation of a seawater intake system was investigated. A digital camera fixed onto a skid was used to record the biogrowth at intervals of 5 m up to a depth of 55 m. Divers inspected the intake shaft and collected the biogrowth samples for biomass estimation. A biomass density of 7.5 kg m-2 and 28.2 kg m-2 was recorded at 5 and 30 m depths respectively. Inspection by the divers revealed that hard-shelled organisms such as oysters and brown and green mussels were observed in plenty up to a thickness of 15 cm and bryozoans grew as epibionts. At lower depths (<40 m), hydroids grew on the shells of green mussels along with silt accumulation. The biofouling community was composed of 46 organisms, exhibiting variation in distribution and abundance. The study explains the extent and type of marine biogrowth phenomena with depth and describes biofouling preventive methods.Supplemental data for this article is available online at https://doi.org/10.1080/08927014.2021.1933457 .

Morphine Versus Loperamide with Intrasite Gel in the Treatment of Painful Dermal Ulcers: A Randomized, Crossover Study.

BACKGROUND: Topical morphine along with intrasite gel has been proven to be a simple and effective method to relieve pain. However, morphine is still not freely available in developing countries due to drug restrictions and stringent laws governing it. Loperamide has been reported to relieve pain caused by stomatitis effectively when given topically. Loperamide, being an mu receptor agonist with no systemic absorption, can serve a dual purpose here. Also loperamide being freely available as an over-the-counter drug can be a surrogate drug for topical application. OBJECTIVES: The primary aim was to compare the efficacy of loperamide and morphine in treating pain when applied topically along with intrasite gel. STUDY DESIGN: Adult patients with healthy wounds with pain on Numeric Rating Scale (NRS-11) greater than 5 with no systemic comorbid illness were divided randomly into 2 groups - group morphine or group loperamide - for 24 hours followed by a 1-day washout and crossover in the other group for 24 hours. Pain was assessed once every day. SETTING: Medical college and hospital. METHODS: The parameters assessed included: (1) characteristics of the ulcer; (2) pain was assessed by NRS-11 at 12-hour intervals for a period of 72 hours; and (3) patient satisfaction. Statistical analysis used repeated measures analysis of variance to measure change in mean NRS-11 within each group. Analysis of covariance was used to compare the mean change in NRS-11 in the 2 groups. RESULTS: Morphine and loperamide were equivocal in pain relief after 12 and 24 hours (P = 0.400 and P = 0.753); however, the patient satisfaction scores were better in the morphine group. LIMITATIONS: The earlier studies performed used injectable forms of morphine, for the sake of comparison, we used powdered morphine and powdered Loperamide diluted with saline. Confounding variables include ulcer size and aetiology, which can be a source of bias. The ulcer size was not standardized due to the paucity of sample to study. Equianalgesic doses of loperamide and morphine could not be found even after an extensive literature search. The loperamide dose used in our case was equal to the dose used orally since the same dose appears effective across a range of oral opioid analgesics. The morphine dose was standardized as 10 mg based on a mixture previously used to treat pain due to epidermolysis bullosa. CONCLUSIONS: Topical loperamide can be an efficacious and novel intervention to treat painful ulcers while avoiding systemic effects.

Elucidating a Thermoresponsive Multimodal Photo-Chemotherapeutic Nanodelivery Vehicle to Overcome the Barriers of Doxorubicin Therapy.

In an attempt to circumvent the major pitfalls associated with conventional chemotherapy including drug resistance and off-target toxicity, we have adopted a strategy to simultaneously target both mitochondrial DNA (Mt-DNA) and nuclear DNA (n-DNA) with the aid of a targeted theranostic nanodelivery vehicle (TTNDV). Herein, folic acid-anchored p-sulfo-calix[4]arene (SC4)-capped hollow gold nanoparticles (HGNPs) were meticulously loaded with antineoplastic doxorubicin (Dox) and its mitochondrion-targeted analogue, Mt-Dox, in a pretuned ratio (1:100) for sustained thermoresponsive release of cargo. This therapeutic strategy was enabled to eradicate both n-DNA and Mt-DNA leaving no space to develop drug resistance. The SC4-capped HGNPs (HGNPSC4) were experimented for the first time as a photothermal (PTT) agent with 61.6% photothermal conversion efficiency, and they generated tunable localized heat more efficiently than bare HGNPs. Moreover, the cavity of SC4 facilitated the formation of an inclusion complex with folic acid to target the folate receptor expressing cancer cells and imparted enhanced biocompatibility. The as-synthesized TTNDV was demonstrated to be an ideal substrate for surface-enhanced Raman scattering (SERS) to monitor the molecular-level therapeutic progression in cells and a spheroidal model. A significant reduction in the tumor mass with a marked survival benefit was achieved in syngraft murine models through this synergistic photo-chemotherapy. Collectively, this multifunctional nanoplatform offers a robust approach to treat cancer without any scope of generating Dox resistance and off-target toxicity.

Targeted Theranostic Nano Vehicle Endorsed with Self-Destruction and Immunostimulatory Features to Circumvent Drug Resistance and Wipe-Out Tumor Reinitiating Cancer Stem Cells.

The downsides of conventional cancer monotherapies are profound and enormously consequential, as drug-resistant cancer cells and cancer stem cells (CSC) are typically not eliminated. Here, a targeted theranostic nano vehicle (TTNV) is designed using manganese-doped mesoporous silica nanoparticle with an ideal surface area and pore volume for co-loading an optimized ratio of antineoplastic doxorubicin and a drug efflux inhibitor tariquidar. This strategically framed TTNV is chemically conjugated with folic acid and hyaluronic acid as a dual-targeting entity to promote folate receptor (FR) mediated cancer cells and CD44 mediated CSC uptake, respectively. Interestingly, surface-enhanced Raman spectroscopy is exploited to evaluate the molecular changes associated with therapeutic progression. Tumor microenvironment selective biodegradation and immunostimulatory potential of the MSN-Mn core are safeguarded with a chitosan coating which modulates the premature cargo release and accords biocompatibility. The superior antitumor response in FR-positive syngeneic and CSC-rich human xenograft murine models is associated with a tumor-targeted biodistribution, favorable pharmacokinetics, and an appealing bioelimination pattern of the TTNV with no palpable signs of toxicity. This dual drug-loaded nano vehicle offers a feasible approach for efficient cancer therapy by on demand cargo release in order to execute complete wipe-out of tumor reinitiating cancer stem cells.

Diagnostic spectro-cytology revealing differential recognition of cervical cancer lesions by label-free surface enhanced Raman fingerprints and chemometrics.

Herein we have stepped-up on a strategic spectroscopic modality by utilizing label free ultrasensitive surface enhanced Raman scattering (SERS) technique to generate a differential spectral fingerprint for the prediction of normal (NRML), high-grade intraepithelial lesion (HSIL) and cervical squamous cell carcinoma (CSCC) from exfoliated cell samples of cervix. Three different approaches i.e. single-cell, cell-pellet and extracted DNA from oncology clinic as confirmed by Pap test and HPV PCR were employed. Gold nanoparticles as the SERS substrate favored the increment of Raman intensity exhibited signature identity for Amide III/Nucleobases and carotenoid/glycogen respectively for establishing the empirical discrimination. Moreover, all the spectral invention was subjected to chemometrics including Support Vector Machine (SVM) which furnished an average diagnostic accuracy of 94%, 74% and 92% of the three grades. Combined SERS read-out and machine learning technique in field trial promises its potential to reduce the incidence in low resource countries.

Surface charge modulates the internalization vs. penetration of gold nanoparticles: comprehensive scrutiny on monolayer cancer cells, multicellular spheroids and solid tumors by SERS modality.

Precise control over the dynamics of nanoparticles (NPs) in a tumor microenvironment is highly warranted for the development of an efficient nanotheranostic agent. Even though inductively coupled plasma mass spectrometry can provide a quantitative assessment regarding the uptake efficiency of metal NPs, enumeration of deep tissue penetration capacity remains as a challenge. Herein, we have demonstrated an accurate tracking of the uptake efficiency and penetration phenomenon of gold nanoparticles (AuNPs: 40-50 nm) with respect to three different surface charges in monolayer (2D) cells, multicellular spheroids (3D) and in vivo tumors by surface-enhanced Raman spectroscopy (SERS). While positively charged AuNPs showed around two-fold increased internalization in monolayer cells, SERS-tag-based line scanning on multi-layered tumor spheroids illustrated almost nine-fold superior penetration capability with negatively charged AuNPs. Further, the enhanced solid tumor distribution contributed by the negatively charged AuNPs could appreciably escalate its clinical utility in cancer management.

Tracking the Footprints of Paclitaxel Delivery and Mechanistic Action via SERS Trajectory in Glioblastoma Cells.

The design and development of an efficacious tumor-specific drug-delivery system is a challenging task. In this study, we have synthesized target-specific small peptide substrates on an octaguanidine sorbitol scaffold, named small molecular targeted drug-delivery conjugate (SMTDDC). The SMTDDC fabrication, with dual targeting cRGD and Cathepsin B (Cath B)-specific tripeptide (Glu-Lys-Phe), altered the microtubule network of glioblastoma cells by the orchestrated release of the cytotoxic paclitaxel (PTX). Cath B assisted PTX delivery was monitored by high-performance liquid chromatography and Surface-Enhanced Raman Scattering (SERS) modalities. The time-dependent SERS fingerprinting and imaging revealed a fast and accurate PTX release profile and subsequent in vitro cytotoxicity as well as the apoptotic events and microtubule network alteration in U-87 MG glioblastoma cells. Furthermore, SMTDDC displayed adequate stability under physiological conditions and demonstrated biocompatibility toward red blood cells and lymphocytes. This study indicated a new insight on SERS-guided peptidomimetic sorbitol molecular transporter, enabling a greater promise with high potential for the further development of PTX delivery in glioblastoma treatment.

Biogenic Ag Nanoparticles from Neem Extract: Their Structural Evaluation and Antimicrobial Effects against Pseudomonas nitroreducens and Aspergillus unguis (NII 08123).

Silver nanocrystals have been successfully fabricated by the bioreduction route using the ethanolic extract of Azadirachta indica (neem) leaves as the reducing and capping agent without solvent interference. The silver nanocrystals were grown in a single-step method, without the influence of external energy or surfactants, and at room temperature. The nanoparticles were prepared from different ratios of silver ions to reducing agent molecules and were characterized by UV-vis spectroscopy and transmission electron microscopy (TEM). The nanoparticles were roughly spherical and polydispersed with diameters of less than 40 nm, as determined with high-resolution transmission electron microscopy (HRTEM). Fast Fourier transform (FFT) analysis and X-ray diffraction (XRD) analysis elucidated the crystalline nature of the nanoparticles. The presence of participating functional groups was determined with Fourier transform infrared (FTIR) spectroscopy. The synthesized silver nanoparticles were analyzed as a potential surface-enhanced Raman spectroscopy (SERS) substrate by incorporating rhodamine B as the Raman reporter molecule. The bioreduction process was monitored through SERS fingerprint, which was evaluated by the change in vibrational energies of metal-ligand bonds. It was possible to detect the SERS spectral pattern of the probe molecules on the Ag nanoparticles without the use of any aggregating agent. Thus, the formation of probable intra- and interparticle hot spots was attributed to evaporation-induced aggregation. Furthermore, stirring and precursor salt concentration influenced the kinetics involved in the fabrication process. The thermal stability of the lyophilized nanoparticles prepared from 0.1 M AgNO3 was evaluated with thermogravimetric analysis (TGA) and had a residual mass of 60% at 600 °C. X-ray photoelectron spectroscopy (XPS) studies were used to validate the compositional and chemical-state information. The biomass-capped silver nanoparticles provided antimicrobial activity by inhibiting the growth of Pseudomonas nitroreducens, a biofilm-forming bacterium, and the fungus, Aspergillus unguis (NII 08123).

Functional evaluation of a monotreme-specific antimicrobial protein, EchAMP, against experimentally induced mastitis in transgenic mice.

EchAMP, the tenth most abundant transcript expressed in the mammary gland of echidna, has in vitro broad-spectrum antibacterial effects. However, the effects of EchAMP on mastitis, a condition where inflammation is triggered following mammary gland infection, has not been investigated. To investigate the impact of EchAMP against mastitis, EchAMP transgenic mice were generated. In antibacterial assays, the whey fractions of milk from transgenic mice significantly reduced growth of Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa compared with whey fractions from wildtype mice. Furthermore, a mastitis model created by infecting mammary gland with these four bacterial strains displayed a significant reduction in bacterial load in transgenic mice injected with S. aureus and B. subtilis. On further confirmation, histomorphologic analysis showed absence of necrosis and cell infiltration in the mammary glands of transgenic mice. To understand the role of EchAMP against inflammation, we employed an LPS-injected mastitis mouse model. LPS is known to induce phopshorylation of NF-κB and MAPK pathways, which in turn activate downstream proinflammatory signaling mediators, to promote inflammation. In LPS-treated EchAMP transgenic mice, phosphorylation levels of NF-κB, p38 and ERK1/2 were significantly downregulated. Furthermore, in mammary gland of transgenic mice, there was a significant downregulation of mRNA levels of proinflammatory cytokines, namely TNF-α, IL-6 and IL-1ß. Taken together, these data suggest that EchAMP has an antiinflammatory response and is effective against S. aureus and B. subtilis. We suggest that EchAMP may be a potential prophylactic protein against mastitis in dairy animals by expressing this gene in their mammary gland.

Exploring Mitochondria-Mediated Intrinsic Apoptosis by New Phytochemical Entities: An Explicit Observation of Cytochrome c Dynamics on Lung and Melanoma Cancer Cells.

Hydnocarpin (Hy) is a flavonoid isolated and purified from the seeds of Hydnocarpus wightiana Blume. Herein, we have developed a built-in semi-synthetic modification on Hy by one-pot multi-component reaction and a [3 + 2] cycloaddition strategy to append five membered isoxazole and isoxazolone as new phytochemical entities (NPCEs). Two selected NPCEs viz Hy-ISO-VIII and Hy-ISO-G from the library of 20 newly synthesized derivatives after in vitro screening unveiled promising cytotoxicity and induced caspase-mediated apoptosis against the human lung and melanoma cancer cells which were well supported by virtual screening based on ligand binding affinity and molecular dynamic simulations. As a new insight, we introduced surface-enhanced Raman spectroscopy to identify the chemo-marker molecular fingerprint to confirm the cellular uptake, cytochrome c release, and DNA fragmentation in a label-free manner. The present findings throw up a surfeit of seminal reasons behind the semi-synthetic modification of Hy, stepping forward to cancer chemotherapy.

Biogenic Cluster-Encased Gold Nanorods as a Targeted Three-in-One Theranostic Nanoenvelope for SERS-Guided Photochemotherapy against Metastatic Melanoma.

Effective treatment of malignant melanoma requires an appropriate combination of therapeutic intervention with long-term prognosis as it often survives by monotherapies. Herein, we report a novel melanoma-targeted theranostic nanoenvelope (MTTNe: ISQ@BSA-AuNC@AuNR@DAC@DR5) which has been constructed by assembling a bovine serum albumin (BSA) stabilized gold nanocluster on a gold nanorod (BSA-AuNC@AuNR), a three-in-one theranostic modality, i.e., photothermal therapy (PTT), photodynamic therapy (PDT), and chemotherapy, tethered with a surface-enhanced Raman scattering (SERS) detection technique. The resultant MTTNe was coloaded with the melanoma-specific FDA approved drug dacarbazine (DAC) and a newly synthesized near-infrared (NIR) absorbing squaraine molecule ISQ that served partly as a photosensitizer and multiplex Raman reporter. Finally, a nanoenvelope was anchored with anti-DR5 monoclonal antibodies as a targeting motif for highly expressed melanoma-specific death receptors in malignant cells. Significant phototherapies of MTTNe were initiated upon an 808 nm single laser trigger which showed a synergistic effect of photothermal hyperthermia as well as singlet oxygen (1O2) driven photodynamic effect in the presence of ISQ followed by on-demand thermoresponsive drug release in the intracellular milieu. Moreover, a multiplex SERS spectral pattern of ISQ (1345 cm-1) and DAC (1269 cm-1) has been utilized for monitoring precise drug release kinetics and target-specific recognition on melanoma cells by Raman imaging. Therapeutic performance of the nanoenvelope was evaluated by in vitro cytotoxicity studies in human melanoma cells (A375) and confirmed the apoptotic phenomenon by molecular-level monitoring of intracellular SERS fingerprints. Finally, to address the biocompatibility of MTTNe, in vivo subacute toxicity was conducted on BALB/c mice. Hence, the current studies mark a footstep of a facile strategy for the treatment of melanoma by synergistic multimodal photothermal/photodynamic/chemotherapy.